Cancer Drug Shows Potent Activity in the Lab Against SARS-CoV-2, Including B.1.1.7 Variant
Scientists from the Quantitative Bioscience Institute (QBI) at the University of San Francisco and the Icahn School of Medicine at Mt. Sinai (ISMMS) in New York, have shown that plitidepsin (Aplidin), a drug approved by the Australian Regulatory Agency for the treatment of multiple myeloma, has potent antiviral activity against CoV-2-SARS.
Flitidepsin
Laboratory experiments reported that plitidepsin, a compound originally discovered in a Mediterranean sea squirt, was 27.5 times more potent against CoV-2-SARS than remdesivir, a drug that received FDA approval in 2020 for the treatment of VID-CoV-19. In addition, in two preclinical models of COVID-19, plitidepsin showed a 100-fold reduction in viral replication in the lungs and demonstrated an ability to reduce lung inflammation.
In a separate publication published on the bioRxiv pre-printing server, researchers from UCSF and ISMMS, in collaboration with Greg Towers, PhD, and Clare Jolly, PhD, from University College London, show that plitidepsin has antiviral activity against the newly identified variant B.1.1.7 of SARS-CoV-2, which is comparable to the drug's activity against the original strain of SARS-CoV-2. In addition, they found that plitidepsin is approximately 100 times more potent than remesivir in human epithelial cells.
Our preclinical data showing increased potency over remdesivir, and in conjunction with the first recent clinical data showing promising results in patients with COVID-19, as indicated by the manufacturer of this drug, suggest that plitidepsin should be further evaluated as a therapy for COVID-19″.
It will not develop resistance
The studies were conducted in close collaboration with PharmaMar, a Spanish pharmaceutical company that was the first to isolate plitidepsin (commercial name Aplidin) from a marine organism known as Aplidium albicans.
"Plitidepsin is an extremely potent inhibitor of CoV-2-SARS, but its main advantage is that it targets a host protein rather than a viral protein," said Kris White, PhD, Assistant Professor of Microbiology and first author of the scientific paper. "This means that if plitidepsin is successful in treating COVID-19, it will not be able to develop resistance against it by mutation, which is a major concern with the spread of new variants from the UK and South Africa.
"It is the host mechanisms that allow SARS-CoV-2 to wreak havoc," said Dr. Krogan. "By targeting the host factors that enable or facilitate this disease, we have the potential to have a greater impact in drug development. In this case, CoV-2-SARS and its mutant strains, and possibly other viruses that follow the same pathway, may also be susceptible to the same therapeutic agents that inhibit this virus-host interaction.
